1. Field of the Invention
The present invention relates to a system and process for producing particles such as nanoparticles. More particularly, the invention relates to a continuous process for producing monodispersed microparticles and/or nanoparticles using a fiber fluidic system.
2. Description of Related Art
Nanoparticles (NPs) are insoluble materials that can range in size from about 1 nm to about 100 nm. In some cases, NPs may have a size that ranges from about 5 nm to about 1 μm. The small size and high surface area of NPs make them highly suitable for certain biomedical applications. The small size of NPs gives them the ability to be injected locally or systemically, extravasate into diseased tissues, enter cells, and interact with targets at the molecular level; providing a range of useful biomedical opportunities. The high surface area of NPs enables faster and stronger interaction with targets than with macro-scaled counterparts. Additionally, the macromolecular size of NPs allows them to act as carriers for the delivery of high payloads of drugs or contrast agents. NPs also allow surface functionalization with ligands that overcome physiological barriers and provide targeting ability. With such properties, it is understood that NP-based technologies may have the potential to enable the development of new diagnostic, therapeutic, and theranostic technologies that offer higher efficacy, bioavailability, individualization, and safety compared to current technologies.
Currently, there have been only a few NP-based systems used as therapeutic or biotechnological tools. It is expected, however, that nanotechnology will play an increasing role in health care and biomedicine in the near future. FDA-approved NP-based therapeutics currently include liposomal formulations of doxorubicin (Doxil®), daunorubicin (DaunoXome®), and amphotericin B (Abelcet®, Amphotec®, and AmBisome®), as well as albumin-based protein NPs for paclitaxel delivery (Abraxane®). Despite the high versatility and long history of polymeric materials in medicine, to date no polymeric NP-based therapeutic systems have been commercialized. There are, however, currently many ongoing clinical trials involving NPs, many of which are related to cancer therapeutics.
In the area of diagnostics, polymeric NPs have applications as contrast agents for in vivo, ex vivo, or in vitro biomarker/pathogen detection and imaging. NPs may also have applications as capture agents for the separation of biomolecules. NPs may also be incorporated into nanocomposites or coatings in medical devices (including drug eluting stents, tissue engineered scaffolds, or antibacterial coatings) that require controlled release of active agents, nanotexturing, or high porosity for enhanced physiological interaction and response.
In the area of biotechnology, polymeric NPs may also have significant applications in bioseparations. NPs may be used as templates for preparation of porous media for the separation of biomolecules via electrophoresis. In these materials, stimuli-responsive NPs may provide tunable porosity. In such applications, NP monodispersity may be critical for analytical reproducibility.
Two main approaches have been typically used for the preparation of NPs. Top-down approaches such as wet milling utilize mechanical work to create small particles from larger materials. In contrast, bottom-up approaches (such as polymerization, emulsification, or precipitation) result in the formation of NPs by assembly of smaller building blocks. Forming NPs by such methods enables greater control over the resulting architecture and properties of the NP. In the bottom-up method, NPs are typically prepared by the introduction of a precursor phase (monomers or polymers) into a second continuous phase in the form of a dispersion or emulsion. NP formation then may occur through the precipitation, gelation, or polymerization of the precursors. Encapsulation of active agents is carried out by inclusion of said agent within the polymer-rich phase, which results in the entrapment of the agent upon NP solidification.
While such synthetic methods have been widely used at the laboratory scale, scale-up issues for commercialization have been common due to the difficulty in providing homogenous mixing in bulk processes, which leads to highly polydispersed (inhomogeneous) NP populations. In addition, these methods may require very high energy mixing that can prevent their use for the encapsulation of labile active agents such as protein therapeutics. The monodispersity of NP suspensions plays a key role in the effectiveness of NPs in a number of applications, including biomedicine. Although laboratory processes for reproducible synthesis of polymeric particles (e.g., NPs) through emulsion and nanoprecipitation methods have matured, the development of suitable methods for synthesis of monodispersed NPs on the scales required for commercialization has not yet been achieved. Thus, it is important to develop new processes that could enable the reproducible preparation of NPs on a large scale.
Fiber Film® Contactors (FCCs) were first introduced by Merichem Company (Houston, Tex., U.S.A.) as an improved method for caustic washing of petroleum that avoids the formation of emulsions. The contactor in an FCC can be filled with 8 μm to 120 μm diameter fibers that are oriented along the length of the pipe. A fiberphilic phase is first introduced to the FCC, which forms a constrained film around the fibers driven by polarity and surface tension. Typically, a 0.25 μm to 4 μm thick aqueous phase forms a sheath around hydrophilic fibers. Next, a free phase is introduced downstream and forced to flow in between the coated fibers. In extraction processes, the two phases are immiscible, which results in a filming process that creates a large interfacial surface area. This surface area is continuously renewed for highly efficient extraction. The fact that an emulsion is never formed is beneficial as immediate phase separation can occur upon exit from the FCC.